Process for manufacturing haloacetamides

Abstract

The present invention relates to a process for manufacturing haloacetamides of formula (I), ##STR00001##
comprising sub-step (a): reacting halones of formula (II) with oleum; followed by sub-step (b): reacting the reaction mixture obtained in sub-step (a) with an amine of formula (IV) optionally in the presence of a base;
wherein the variables are defined according to the description.

Claims

1. A process for manufacturing haloacetamides of formula (I), ##STR00013## wherein L is halogen; R.sup.1 is halogen; R.sup.2 is H or halogen; R.sup.A is selected from the group consisting of H, C.sub.1-C.sub.6-alkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-cyanoalkyl, C.sub.1-C.sub.6-nitroalkyl, C.sub.1-C.sub.6-hydroxyalkyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.6-alkyl, amino-C.sub.1-C.sub.6-alkyl, (C.sub.1-C.sub.6-alkyl)amino-C.sub.1-C.sub.6-alkyl, di(C.sub.1-C.sub.6-alkyl)amino-C.sub.1-C.sub.6-alkyl, C.sub.3-C.sub.6-cycloalkyl, phenyl and benzyl, wherein the phenyl and the benzyl ring independently of one another are unsubstituted or substituted with 1 to 5 substituents selected from the group consisting of halogen, NO.sub.2, C.sub.1-C.sub.6-alkyl and C.sub.1-C.sub.6-alkoxy; and R.sup.B is selected from the group consisting of C.sub.1-C.sub.6-alkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.1-C.sub.6-cyanoalkyl, C.sub.1-C.sub.6-nitroalkyl, C.sub.1-C.sub.6-hydroxyalkyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.6-alkyl, amino-C.sub.1-C.sub.6-alkyl, (C.sub.1-C.sub.6-alkyl)amino-C.sub.1-C.sub.6-alkyl, di(C.sub.1-C.sub.6-alkyl)amino-C.sub.1-C.sub.6-alkyl, C.sub.3-C.sub.6-cycloalkyl, phenyl and benzyl, wherein the phenyl and the benzyl ring are independently of one another unsubstituted or substituted with 1 to 5 substituents selected from the group consisting of halogen, NO.sub.2, C.sub.1-C.sub.6-alkyl and C.sub.1-C.sub.6-alkoxy; or R.sup.A and R.sup.B together with the N atom which they are attached to, represent a saturated or aromatic 3- to 6-membered ring, optionally containing 1 to 3 additional heteroatoms selected from the group consisting of O, S and N, with the ring optionally being substituted with 1 to 3 C.sub.1-C.sub.6-alkyl substituents; comprising sub-step (a): reacting halones of formula (II), ##STR00014## wherein L, R.sup.1 and R.sup.2 are defined as in formula (I); L.sup.1 and L.sup.2 independently of one another are halogen; and L.sup.3 is fluorine; with oleum; followed by sub-step (b): reacting the reaction mixture obtained in sub-step (a) with an amine of formula (IV) ##STR00015## or a salt thereof, wherein R.sup.A is selected from the group consisting of H, C.sub.1-C.sub.6-alkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-cyanoalkyl, C.sub.1-C.sub.6-nitroalkyl, C.sub.1-C.sub.6-hydroxyalkyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.6-alkyl, amino-C.sub.1-C.sub.6-alkyl, (C.sub.1-C.sub.6-alkyl)amino-C.sub.1-C.sub.6-alkyl, di(C.sub.1-C.sub.6-alkyl)amino-C.sub.1-C.sub.6-alkyl, C.sub.3-C.sub.6-cycloalkyl, phenyl and benzyl, wherein the phenyl and the benzyl ring independently of one another are unsubstituted or substituted with 1 to 5 substituents selected from the group consisting of halogen, NO.sub.2, C.sub.1-C.sub.6-alkyl and C.sub.1-C.sub.6-alkoxy; R.sup.B is selected from the group consisting of C.sub.1-C.sub.6-alkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.1-C.sub.6-cyanoalkyl, C.sub.1-C.sub.6-nitroalkyl, C.sub.1-C.sub.6-hydroxyalkyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.6-alkyl, amino-C.sub.1-C.sub.6-alkyl, (C.sub.1-C.sub.6-alkyl)amino-C.sub.1-C.sub.6-alkyl, di(C.sub.1-C.sub.6-alkyl)amino-C.sub.1-C.sub.6-alkyl, C.sub.3-C.sub.6-cycloalkyl, phenyl and benzyl, wherein the phenyl and the benzyl ring are independently of one another unsubstituted or substituted with 1 to 5 substituents selected from the group consisting of halogen, NO.sub.2, C.sub.1-C.sub.6-alkyl and C.sub.1-C.sub.6-alkoxy; or R.sup.A and R.sup.B together with the N atom which they are attached to, represent a saturated or aromatic 3- to 6-membered ring, optionally containing 1 to 3 additional heteroatoms from the group O, S and N, with the ring optionally being substituted with 1 to 3 C.sub.1-C.sub.6-alkyl substituents; optionally in the presence of a base.

2. The process of claim 1, wherein R.sup.A is H, C.sub.1-C.sub.4-alkyl or C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.4-alkyl; and R.sup.B is C.sub.1-C.sub.4-alkyl or C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.4-alkyl.

3. The process of claim 1, wherein sub-step (a) is carried out in the absence of any additional solvent.

4. The process claim 1, wherein in sub-step (a) the halones of formula (II) are initially charged in a reaction vessel and subsequently the oleum is added into the reaction vessel.

5. The process of claim 1, wherein in sub-step (a) the oleum and the halones of formula (II) are reacted in a pressure-vessel.

6. The process of claim 1, wherein the intermediate of formula (III) ##STR00016## wherein L, R.sup.1, R.sup.2 and L.sup.3 are defined as in claim 1; obtained in sub-step (a) is directly distilled off the reaction mixture obtained in sub-step (a), and transferred directly into the reactor used for sub-step (b).

7. The process of claim 1, wherein sub-step (b) is carried out in an additional solvent selected from ethers, or mixtures of ethers with other solvents selected from the group consisting of aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons, nitriles, ketones and dipolar aprotic solvents.

8. The process of claim 1, wherein in sub-step (b) the amines of formula (IV) are employed.

Description

EXAMPLES

1. Preparation of 2-bromo-2,2-difluoro-N,N-dimethyl-acetamide

(1) ##STR00012##

Example 1.1

(2) 40.0 g (0.14 mol) 1,2-dibromo-1-chloro-1,2,2-trifluoroethane, Freon 113B2 (97%) were placed in a 250 mL 4-necked flask equipped with a flexible Teflon tube connected with a second 500 mL reactor filled with a pre-cooled solution (12 C.) of dimethylamine in THF (2.0 M, 250 mL) Oleum (65%, 34.6 g, 0.28 mol) was added to the Freon 113B over the course of 15 min at 22 to 24 C.

(3) After some initiation period, the exothermic reaction slowly started which could be detected by the occurrence of brown fumes and the condensation of a colorless liquid at the cold parts of the flask. The reaction temperature was kept at 24 C. for two hours. Thereafter, the temperature was increased to 80 C. over the course of 6 h. The reaction mixture was kept at that temperature overnight.

(4) Afterwards, the mixture was heated to 130 C. and the remainder distilled off.

(5) The mixture in the second reactor was rectified over a 10 cm Vigreux column. The first fraction was distilled off under normal pressure and consisted of THF and low boiling side components.

(6) The residue was distilled under reduced pressure (20-5 mbar) at 80-135 C. The first fraction was obtained as a colorless liquid (25.9 g; yield: 77%; purity: >85%)

Example 1.2

(7) 120.0 g (0.42 mol) 1,2-dibromo-1-chloro-1,2,2-trifluoroethane, Freon 113B2 (97%) were placed in a 500 mL Hastelloy C pressure reactor equipped with a flexible Teflon tube connected with a second 1 L reactor containing a pre-cooled solution (12 C.) of dimethylamine in THF (2.0 M, 526 mL). Oleum (65%, 88.2 g, 0.72 mol) was added to the Freon 113B at 10 C. The pressure reaction was heated to 60 C. The reaction temperature was kept at 60 C. for two hours. A pressure of 5.5 bar was reached during the reaction. Thereafter, the pressure reactor was cooled to 15 C. and the pressure was released over the Teflon tube to the second reactor.

(8) Afterwards, the pressure reactor was heated to 130 C. and the remainder distilled off. The mixture in the second reactor was rectified over a 10 cm Vigreux column. The first fraction was distilled off under normal pressure and consists of THF and low boiling side components. The residue was distilled under reduced pressure (20-5 mbar) at 80-135 C. The first fraction was obtained as a colorless liquid (100.5 g; yield: 90.1%; purity: 76.3%).

Example 1.3

(9) 120.0 g (0.42 mol) 1,2-dibromo-1-chloro-1,2,2-trifluoroethane, Freon 113B2 (97%) were placed in a 500 mL Hastelloy C pressure reactor equipped with a flexible Teflon tube connected with a second 1 L reactor containing a pre-cooled solution (12 C.) of dimethylamine in THF (2.0 M, 526 mL). Oleum (65%, 88.2 g, 0.72 mol) was added to the Freon 113B at 10 C. The pressure reaction was heated to 50 C. The reaction temperature was kept at 50 C. for four hours. A pressure of 4.0 bar was reached during the reaction. Thereafter, the pressure reactor was cooled to 15 C. and the pressure was released over the Teflon tube to the second reactor.

(10) Afterwards, the pressure reactor was heated to 130 C. and the remainder distilled off.

(11) The mixture in the second reactor was rectified over a 10 cm Vigreux column. The first fraction was distilled off under normal pressure and consists of THF and low boiling side components. The residue was distilled under reduced pressure (20-5 mbar) at 80-135 C. The first fraction was obtained as a colorless liquid (97.8 g; yield: 87.8%; purity: 76.4%)

Example 1.4

(12) 120.0 g (0.42 mol) 1,2-dibromo-1-chloro-1,2,2-trifluoroethane, Freon 113B2 (97%) were placed in a 500 mL Hastelloy C pressure reactor equipped with a flexible Teflon tube connected with a second 1 L reactor containing a pre-cooled solution (12 C.) of dimethylamine in THF (2.0 M, 526 mL). Oleum (65%, 88.2 g, 0.72 mol) was added to the Freon 113B at 10 C. The pressure reaction was heated to 40 C. The reaction temperature was kept at 40 C. for 10 h. A pressure of 3.6 bar was reached during the reaction. Thereafter, the pressure reactor was cooled to 15 C. and the pressure was released over the Teflon tube to the second reactor.

(13) Afterwards, the pressure reactor was heated to 130 C. and the remainder distilled off.

(14) The mixture in the second reactor was rectified over a 10 cm Vigreux column. The first fraction was distilled off under normal pressure and consists of THF and low boiling side components. The residue was distilled under reduced pressure (20-5 mbar) at 80-135 C. The first fraction was obtained as a colorless liquid (99.0 g; yield: 87.0%; purity: 74.8%)

Example 1.5

(15) 120.0 g (0.42 mol) 1,2-dibromo-1-chloro-1,2,2-trifluoroethane, Freon 113B2 (97%) were placed in a 500 mL Hastelloy C pressure reactor equipped with a flexible Teflon tube connected with a second 1 L reactor containing a pre-cooled solution (12 C.) of dimethylamine in 1,2-dichloroethane (2.0 M, 526 mL). Oleum (65%, 88.2 g, 0.72 mol) was added to the Freon 113B at 10 C. The pressure reaction was heated to 50 C. The reaction temperature was kept at 50 C. for 4 h. A pressure of 4.4 bar was reached during the reaction. Thereafter, the pressure reactor was cooled to 15 C. and the pressure was released over the Teflon tube to the second reactor.

(16) Afterwards, the pressure reactor was heated to 130 C. and the remainder distilled off. The mixture in the second reactor was rectified over a 10 cm Vigreux column. The first fraction was distilled off under normal pressure and consists of THF and low boiling side components. The residue was distilled under reduced pressure (20-5 mbar) at 80-135 C. The first fraction was obtained as a colorless liquid (81.2 g; yield: 75.9%; purity: 79.6%).

Example 1.6

(17) 120.0 g (0.42 mol) 1,2-dibromo-1-chloro-1,2,2-trifluoroethane, Freon 113B2 (97%) were placed in a 500 mL Hastelloy C pressure reactor equipped with a flexible Teflon tube connected with a second 1 L reactor containing a pre-cooled solution (12 C.) of dimethylamine in diethylether (2.0 M, 540 mL). Oleum (65%, 88.2 g, 0.72 mol) was added to the Freon 113B at 10 C. The pressure reaction was heated to 50 C. The reaction temperature was kept at 50 C. for 4 h. A pressure of 4.4 bar was reached during the reaction. Thereafter, the pressure reactor was cooled to 15 C. and the pressure was released over the Teflon tube to the second reactor.

(18) Afterwards, the pressure reactor was heated to 130 C. and the remainder distilled off.

(19) The mixture in the second reactor was rectified over a 10 cm Vigreux column. The first fraction was distilled off under normal pressure and consists of THF and low boiling side components. The residue was distilled under reduced pressure (20-5 mbar) at 80-135 C. The first fraction was obtained as a colorless liquid (85.3 g; yield: 78.6%; purity: 78.4%).

Example 1.7

(20) 20.0 g (0.074 mol) 1,2-dibromo-1-chloro-1,2,2-trifluoroethane, Freon 113B2 (97%) were placed in a 4-necked flask with a flexible Teflon tube connected with a second 250 L reactor containing a pre-cooled solution (12 C.) of 12.0 g (0.148 mol) dimethylamine.HCl and 40 ml (0.296 mol) triethylamine in dichloromethane (400 mL). Oleum (50%, 14.8 g, 0.092 mol) was added to the Freon 113B at 10 C. After some initiation period, the exothermic reaction slowly started which could be detected by the occurrence of brown fumes and the condensation of a colorless liquid at the cold parts of the flask. The reaction temperature was increase to 80 C. and kept at 80 C. for 20 hours. Thereafter, the content of the second reactor was washed three-times with 100 mL water, the organic phase was dried over MgSO4. Afterwards the solvent was evaporated under reduced pressure.

(21) The residue was distilled under reduced pressure (20-5 mbar) at 80-135 C. The first fraction was obtained as a colorless liquid (11.1 g; yield: 74.2%).